GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis
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PROVIDER: PRJNA904320 | ENA |
REPOSITORIES: ENA
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Project description:Hepatocellular carcinoma (HCC) involves a multistep pathological process in which heterogenous cells are evolved to shape an immunosuppressive microenvironment. Yet it remains largely unknown regarding the specific cell populations and their evolving routes essential for HCC development. Here, we created a rat model mimicking human HCC and generated a single-cell resolution atlas to HCC development. Specifically, we identified three populations of hepatic parenchymal cells during HCC progression, i.e., metabolic hepatocyte (HC Meta ), hepatic progenitor cell-like population with differentiation potential (HPC-like Diff ) and immunosuppressive malignant transformation subset (H-M Immu ). These three distinct subpopulations formed an oncogenic trajectory depicting a dynamic landscape of hepatocyte carcinogenesis, with signature genes reflecting the transition from HPC-like Diff to H-M Immu . Cross-species comparative analysis further revealed the H-M Immu subset to be highly conserved. Importantly, the H-M Immu (GPNMB + Gal-3 + ) cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 was found to be required for the generation of GPNMB + Gal-3 + H-M Immu cells and for their ability to form tumors. Enrichment of GPNMB + Gal-3 + H-M Immu subset was found to be associated with poor prognosis and higher rate of recurrence for HCC patients. Collectively, we unraveled the single-cell evolving mechanism of HCC and uncovered GPNMB + Gal-3 + H-M Immu cells as a major subset contributing to the immunosuppressive microenvironment and HCC malignance
2024-01-02 | GSE243688 | GEO
Project description:Hepatocellular carcinoma (HCC) involves a multistep pathological process in which heterogenous cells are evolved to shape an immunosuppressive microenvironment. Yet it remains largely unknown regarding the specific cell populations and their evolving routes essential for HCC development. Here, we created a rat model mimicking human HCC and generated a single-cell resolution atlas to HCC development. Specifically, we identified three populations of hepatic parenchymal cells during HCC progression, i.e., metabolic hepatocyte (HC Meta ), hepatic progenitor cell-like population with differentiation potential (HPC-like Diff ) and immunosuppressive malignant transformation subset (H-M Immu ). These three distinct subpopulations formed an oncogenic trajectory depicting a dynamic landscape of hepatocyte carcinogenesis, with signature genes reflecting the transition from HPC-like Diff to H-M Immu . Cross-species comparative analysis further revealed the H-M Immu subset to be highly conserved. Importantly, the H-M Immu (GPNMB + Gal-3 + ) cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 was found to be required for the generation of GPNMB + Gal-3 + H-M Immu cells and for their ability to form tumors. Enrichment of GPNMB + Gal-3 + H-M Immu subset was found to be associated with poor prognosis and higher rate of recurrence for HCC patients. Collectively, we unraveled the single-cell evolving mechanism of HCC and uncovered GPNMB + Gal-3 + H-M Immu cells as a major subset contributing to the immunosuppressive microenvironment and HCC malignance
2023-08-10 | GSE218561 | GEO
Project description:GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis.
| PRJNA1019384 | ENA
Project description:Hepatocellular carcinoma (HCC) formation is a multi-step pathological process that involves evolution of a heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins and contribution to HCC development remain largely unknown. Here, comprehensive single-cell transcriptome sequencing was applied to profile rat models of toxin-induced liver tumorigenesis and HCC patients. Specifically, we identified three populations of hepatic parenchymal cells emerging during HCC progression, termed metabolic hepatocytes (HCMeta), Epcam+ population with differentiation potential (EP+Diff) and immunosuppressive malignant transformation subset (MTImmu). These distinct subpopulations form an oncogenic trajectory depicting a dynamic landscape of hepatocarcinogenesis, with signature genes reflecting the transition from EP+Diff to MTImmu. Importantly, GPNMB+Gal-3+ MTImmu cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 is required for the generation and malignant transformation of GPNMB+Gal-3+ MTImmu cells. Enrichment of the GPNMB+Gal-3+ MTImmu subset was found to be associated with poor prognosis and a higher rate of recurrence in patients. Collectively, we unraveled the single-cell HCC progression atlas and uncovered GPNMB+Gal-3+ parenchymal cells as a major subset contributing to the immunosuppressive microenvironment thus malignance in HCC.
| S-SCDT-10_15252-EMBJ_2023114060 | biostudies-other
Project description:Hepatocellular carcinoma (HCC) formation is a multi-step pathological process that involves evolution of a heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins and contribution to HCC development remain largely unknown. Here, comprehensive single-cell transcriptome sequencing was applied to profile rat models of toxin-induced liver tumorigenesis and HCC patients. Specifically, we identified three populations of hepatic parenchymal cells emerging during HCC progression, termed metabolic hepatocytes (HCMeta ), Epcam+ population with differentiation potential (EP+Diff ) and immunosuppressive malignant transformation subset (MTImmu ). These distinct subpopulations form an oncogenic trajectory depicting a dynamic landscape of hepatocarcinogenesis, with signature genes reflecting the transition from EP+Diff to MTImmu . Importantly, GPNMB+ Gal-3+ MTImmu cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 is required for the generation and malignant transformation of GPNMB+ Gal-3+ MTImmu cells. Enrichment of the GPNMB+ Gal-3+ MTImmu subset was found to be associated with poor prognosis and a higher rate of recurrence in patients. Collectively, we unraveled the single-cell HCC progression atlas and uncovered GPNMB+ Gal-3+ parenchymal cells as a major subset contributing to the immunosuppressive microenvironment thus malignance in HCC.
| S-EPMC10711661 | biostudies-literature
Project description:Disruption of skin homeostasis by environmental insults activates pathologic circuitries leading to inflammation and carcinogenesis. Galectin-7 (Gal-7), a lectin preferentially expressed in keratinocytes, has been implicated in wound healing and defective skin repair. Here we report using genetically-engineered mouse models and human samples, essential roles for Gal-7 during skin carcinogenesis via coordinated intracellular and extracellular mechanisms. Heightened Gal-7 expression delineated malignant lesions in non-melanoma skin cancer (NMSC) patients and shaped the course of skin carcinogenesis in mice. Intracellularly, increased Gal-7 conferred genomic instability to skin lesions and favored transcription of inflammation-related genes reprogramming the immune landscape toward a myeloid immunoregulatory profile. Extracellularly, Gal-7 accelerated skin carcinogenesis through glycan-dependent induction of monocytic myeloid-derived suppressor cells with enhanced immune regulatory activity. Our findings identify a lectin-driven molecular circuitry that promotes skin carcinogenesis by coupling genomic instability, transcriptional regulation and myeloid immunosuppressive programs, suggesting a potential therapeutic target for the treatment of NMSC.
2023-01-13 | GSE165285 | GEO
Project description:Accumulation of senescent cells in various tissues has been reported to have a pathological role in age-associated diseases. Inhibition of cellular aging signals prevents the onset of age-associated pathology, but there is a risk of promoting carcinogenesis. Elimination of senescent cells (senolysis) was recently reported to reversibly improve pathological changes related to aging in aged mice without increasing the development of cancer. Here we report that glycoprotein nonmetastatic melanoma protein B (Gpnmb) could be a molecular target for senolytic therapy. Elimination of Gpnmb-positive cells by vaccination improved atherosclerosis.
2021-10-22 | GSE155596 | GEO
Project description:The expression of the soluble protein GPNMB (glycoprotein non-metastatic melanoma protein B) induces an aggressive behavior of tumor cells by promoting proliferation and distant spread. The main molecular feature is the over expression of interleukin Il-33. The gene profile of MCA-1-GPNMB and MCA-1-GPNMB-spheroid cell line was assessed against MCA-1-Mock.
2020-07-30 | E-MTAB-8082 | biostudies-arrayexpress
Project description:Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are conserved carbohydrate-binding proteins that also display RNA-binding activity. We generated mouse embryonic stem cells (mESC) constitutively depleted of Gal-1 and/or Gal-3 using CRISPR-Cas9, and assessed the transcriptomic effects of the individual or concomitant depletion of Gal-1 and Gal-3 in mESCs differentiated by deprivation of the leukaemia inhibitory factor (LIF) for 7 days. Wild-type cells were employed as control.
2023-05-27 | E-MTAB-9262 | biostudies-arrayexpress
Project description:Vibrio harveyi strain:Gal 88 | isolate:Gal 88 Genome sequencing
| PRJNA763340 | ENA